Won Joon Yeon, Kim Dayeon, Park Seon Young, Lee Hye Ran, Lim Jong-Seok, Park Jong Hoon, Song Mi Hyun, Song Hae Ryong, Kim Ok-Hwa, Kim Yonghwan, Cho Tae-Joon
Department of Biological Sciences, Sookmyung Women's University, 100 Cheongpa-ro 47-gil, Yongsan-gu, Seoul, 04310, Republic of Korea.
Division of Pediatric Orthopaedics, Seoul National University Children's Hospital, 101 Daehak-ro, Jongno-gu, Seoul, 03080, Republic of Korea.
BMC Med Genet. 2019 May 3;20(1):70. doi: 10.1186/s12881-019-0802-2.
X-linked spondyloepiphyseal dysplasia tarda (SEDT-XL) is a skeletal disorder characterized by defective structures of vertebral bodies and/or of epiphyses of the long bones, resulting in moderately short stature and early joint degeneration. TRAPPC2 gene, which is important for collagen secretion, has been reported as causative for SEDT-XL.
Here, we report two variants of TRAPPC2 gene of SEDT-XL patients, a missense variant of start codon, c.1A > T, and a deletion variant, c.40delG. To understand molecular consequence of the variants, we establish an in vitro gene expression assay system and demonstrate that both mutated genes are transcribed, but are not properly translated, indicative of the pathogenic nature of those TRAPPC2 variants.
In the current study, we provide additional experimental data showing that loss-of-function TRAPPC2 variants are probably causative for SEDT-XL phenotype. These findings further contribute to the understanding the clinical picture related to TRAPPC2 gene.
X连锁迟发性脊椎骨骺发育不良（SEDT-XL）是一种骨骼疾病，其特征是椎体和/或长骨骨骺结构缺陷，导致身材中度矮小和早期关节退变。据报道，对胶原蛋白分泌很重要的TRAPPC2基因是SEDT-XL的致病原因。
在此，我们报告了SEDT-XL患者TRAPPC2基因的两个变异体，一个起始密码子的错义变异体c.1A>T，以及一个缺失变异体c.40delG。为了解这些变异体的分子后果，我们建立了一个体外基因表达分析系统，并证明两个突变基因都能转录，但不能正确翻译，这表明这些TRAPPC2变异体具有致病性。
在本研究中，我们提供了额外的实验数据，表明功能丧失的TRAPPC2变异体可能是SEDT-XL表型的病因。这些发现进一步有助于理解与TRAPPC2基因相关的临床情况。
